Dual effects of lipophilic extract of Salvia miltiorrhiza (Danshen) on catecholamine secretion in cultured bovine adrenal medullary cells

Ethnopharmacological relevanceSalvia miltiorrhiza (Danshen) is a well known traditional Chinese herb, which has been used widely in China for the treatment of cardiovascular diseases in clinic.Aim of this studyThe aim of the present study is to clarify the effects of lipophilic extract of Salvia miltiorrhiza (LESM) on catecholamine (CA) secretion, a traditional Chinese medicine used widely for the treatment of cardiovascular diseases in China.Materials and methodsLESM was evaluated for its effects on CA secretion using HPLC-ECD method. The effects of LESM on 22Na+ influx and intracellular calcium ([Ca2+]i) were also investigated.ResultsOur results showed that LEMS directly stimulated basal CA secretion in an extracellular Ca2+-dependent manner. And the stimulation was not affected by combination of hexamethonium (Hex), an inhibitor of nAChR. LESM also directly elevated [Ca2+]i. In addition, using selective blockers of voltage-dependent Ca2+ channels, such as nitrendipine (for L-type), ω-agatoxin-IVA (for P-type) and ω-conotoxin-GVIA (for N-type), it was found that nitrendipine suppressed the elevation of [Ca2+]i induced by LESM, but not ω-agatoxin-IVA or ω-conotoxin-GVIA. Compared with acetylcholine (ACh) only, however, combination of LESM with ACh inhibited the raise of CA secretion, 22Na+ influx and [Ca2+]i in a concentration-dependent manner. Furthermore, LESM also inhibited CA secretion induced by veratridine (Ver), and 56 mM K+ at concentrations similar to those for [Ca2+]i rise. One of the lipophilic active compounds, cryptotanshione (Cryp), also had the same effects on CA secretion with LESM.ConclusionsAll these findings suggest that LESM exerts dual effects on CA secretion in cultured bovine adrenal medullary cells. LESM exerts antagonistic effects on nAChR, voltage-dependent Na+ and Ca2+ channels, whereas it is an agonist of L-type Ca2+ channel when it used alone.